J Infect Dis. 2004 Nov 1; 190(9):1692-6.

PubMed ID: 15478077

Correlation between interferon- gamma secretion and cytotoxicity, in virus-specific memory T cells

Horton H, Russell N, Moore E, Frank I, Baydo R, Havenar-Daughton C, Lee D, Deers M, Hudgens M, Weinhold K, McElrath MJ

ELISpot and intracellular cytokine staining are replacing the traditional cytolytic ((51)Cr release) assay method in vaccine trials using human immunodeficiency virus (HIV)-1, and it is widely assumed that the number of interferon (IFN)- gamma -secreting T cells is a surrogate for the level of cytolytic activity. Thus, we sought to determine whether the detection of IFN- gamma in CD8(+) T cells correlates with cytolytic ability in vitro. In 29 (69.0%) of 42 HIV-1-seronegative immunocompetent individuals (22 unvaccinated and 20 vaccinated), virus-specific T cell responses recognizing cytomegalovirus, Epstein-Barr virus, and influenza and HIV-1 Gag epitopes were detected by at least 1 assay method (ELISpot, intracellular cytokine staining, and/or (51)Cr release), and 18 (62.1%) of these 29 demonstrated both IFN- gamma secretion and cytolysis. There was strong correlation between the results of IFN- gamma ELISpot and those of IFN- gamma intracellular cytokine staining ( rho =0.88) and between the results of (51)Cr release and those of intracellular cytokine staining ( rho =0.81); although the correlation is not absolute, intracellular cytokine staining can be used--and is superior to ELISpot--as a surrogate for cytolytic assays.